Clonality analysis of pulmonary tumors by genome-wide copy number profiling

Autoři: Julien P. L. Vincenten aff001;  Hendrik F. van Essen aff003;  Birgit I. Lissenberg-Witte aff004;  Nicole W. J. Bulkmans aff005;  Oscar Krijgsman aff006;  Daoud Sie aff003;  Paul P. Eijk aff003;  Egbert F. Smit aff001;  Bauke Ylstra aff003;  Erik Thunnissen aff008
Působiště autorů: Amsterdam UMC, location VUmc, Department of Pulmonary Diseases, Amsterdam, The Netherlands aff001;  Albert Schweitzer Hospital, Department of Pulmonary Diseases, Dordrecht, The Netherlands aff002;  Amsterdam UMC, location VUmc, Tumor Genome Analysis Core, Cancer Center Amsterdam, The Netherlands aff003;  Amsterdam UMC, location VUmc, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands aff004;  Spaarne Gasthuis, Department of Pathology, Haarlem, The Netherlands aff005;  Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Molecular Oncology & Immunology, Amsterdam, The Netherlands aff006;  Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Thoracic Oncology, Amsterdam, The Netherlands aff007;  Amsterdam UMC, location VUmc, Department of Pathology, Amsterdam, The Netherlands aff008
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


Multiple tumors in patients are frequently diagnosed, either synchronous or metachronous. The distinction between a second primary and a metastasis is important for treatment. Chromosomal DNA copy number aberrations (CNA) patterns are highly unique to specific tumors. The aim of this study was to assess genome-wide CNA-patterns as method to identify clonally related tumors in a prospective cohort of patients with synchronous or metachronous tumors, with at least one intrapulmonary tumor. In total, 139 tumor pairs from 90 patients were examined: 35 synchronous and 104 metachronous pairs. Results of CNA were compared to histological type, clinicopathological methods (Martini-Melamed-classification (MM) and ACCP-2013-criteria), and, if available, EGFR- and KRAS-mutation analysis. CNA-results were clonal in 74 pairs (53%), non-clonal in 33 pairs (24%), and inconclusive in 32 pairs (23%). Histological similarity was found in 130 pairs (94%). Concordance between histology and conclusive CNA-results was 69% (74 of 107 pairs: 72 clonal and two non-clonal). In 31 of 103 pairs with similar histology, genetics revealed non-clonality. In two out of four pairs with non-matching histology, genetics revealed clonality. The subgroups of synchronous and metachronous pairs showed similar outcome for the comparison of histological versus CNA-results. MM-classification and ACCP-2013-criteria, applicable on 34 pairs, and CNA-results were concordant in 50% and 62% respectively. Concordance between mutation matching and conclusive CNA-results was 89% (8 of 9 pairs: six clonal and two non-clonal). Interestingly, in one patient both tumors had the same KRAS mutation, but the CNA result was non-clonal. In conclusion, although some concordance between histological comparison and CNA profiling is present, arguments exist to prefer extensive molecular testing to determine whether a second tumor is a metastasis or a second primary.

Klíčová slova:

Adenocarcinoma of the lung – Adenocarcinomas – Histology – Lung and intrathoracic tumors – Metastasis – Non-small cell lung cancer – Secondary lung tumors – Squamous cell lung carcinoma


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